Our long-range objective is to determine the molecular basis for antiviral resistance. We have recently discovered a factor that interferes with the aminoacylation of viral-RNA but does not appear to affect the normal cellular cognate tRNA; more specifically, this factor appears to cause the discharge of amino acid that has already been esterified to the viral RNA. Using this in vitro phenomenon as an assay we intend to (1) purify the discharging factor(s), (2) characterize the elements of the in vitro reaction, and (3) study the biology of the phenomenon in relation to what is currently known about (a) interferon-stimulated antiviral resistance, (b) antiviral resistance not necessarily related to interferon, and (c) non-antiviral effects of interferon, such as inhibition of cell growth. The biology of the factor(s) will be studied, as appropriate, in normal diploid cells, in cells with chromosomal abnormalities that enhance or depress the response to interferon, cells that are sensitive or resistant to interferon, including cancer cells (especially melanoma lines and carcinoma lines from bladder and lung), and embryonic cells, with regard to uptake, activity, and distribution in intact cells, kinetics of appearance, dose-response relationships, and effects of metabolic or natural tissue inhibitors. The investigations proposed are a detailed analysis of the phenomenon and its possible relationship to several biological phenomena involving natural and induced resistance to viruses of plants, animals, and human beings.